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Norepinephrine is released when a host of physiological changes are activated by a stressful event.

In the brain, this is caused in part by activation of an area of the brain stem called the locus ceruleus. This nucleus is the origin of most norepinephrine pathways in the brain. Noradrenergic neurons project bilaterally (send signals to both sides of the brain) from the locus ceruleus along distinct pathways to many locations, including the cerebral cortex, limbic system, and the spinal cord, forming a neurotransmitter system.

Norepinephrine is synthesized from tyrosine as a precursor, and packed into synaptic vesicles. It performs its action by being released into the synaptic cleft, where it acts on adrenergic receptors, followed by the signal termination, either by degradation of norepinephrine, or by uptake by surrounding cells.

Norepinephrine performs its actions on the target cell by binding to and activating adrenergic receptors. The target cell expression of different types of receptors determines the ultimate cellular effect, and thus epinephrine has different actions on different cell types.

Norepinephrine may be used for the indications attention-deficit/hyperactivity disorder, depression and hypotension. Norepinephrine , as with other catecholamines, itself cannot cross the blood-brain barrier , so drugs such as amphetamines are necessary to increase brain levels.

Norepinephrine, along with dopamine, has come to be recognized as playing a large role in attention and focus. For people with ADD/ADHD, psychostimulant medications such as Ritalin/Concerta (methylphenidate), Dexedrine (dextroamphetamine), and Adderall (a mixture of dextroamphetamine and racemicamphetamine salts) are prescribed to help increase levels of norepinephrine and dopamine. Strattera (atomoxetine) is a selective norepinephrine reuptake inhibitor, and is a unique ADD/ADHD medication, as it affects only norepinephrine, rather than dopamine. As a result, Strattera has a lower abuse potential. However, it may not be as effective as the psychostimulants are with many people who have ADD/ADHD. Consulting with a physician or nurse practitioner is needed to find the appropriate medication and dosage. (Other SNRIs, currently approved as antidepressants, have also been used off-label for treatment of ADD/ADHD.)

Tricyclic antidepressants (TCAs) increase norepinephrine activity as well. Most of them also increase serotonin activity, but tend to have side effects due to the nonspecific activation of histamine and acetylcholine receptors. Side effects include tiredness, increased hunger, dry mouth, and blurred vision. For this reason, they have largely been replaced by newer selective reuptake drugs such as Prozac.

Norepinephrine is also used as a vasopressor medication (for example, brand name Levophed) for patients with critical hypotension. It is given intravenously and acts on both alpha-1 and alpha-2 adrenergic receptors to cause vasoconstriction. Its effect in vitro is often limited to the increasing of blood pressure through agonistic activity on alpha-1 and alpha-2 receptors and causing a resultant increase in peripheral vascular resistance. In high dose and especially when it is combined with other vasopressors, it can lead to limb ischemia and limb death. (Thus, in many nursing and paramedic schools, the phrase "Levophed'll leave them dead" is used.) Norepinephrine is mainly used to treat patients in vasodilatory shock states such as septic shock and neurogenic shock and has shown a survival benefit over dopamine.